Clinical and economic impact of an alert system in primary care for the detection of patients with chronic hepatitis C.

INTRODUCTION: Prevalence of chronic hepatitis C (CHC) is higher in patients born between 1955-1975. The aim was to perform an economic evaluation of an age-based electronic health record (EHR) alert in primary care to detect patients with undiagnosed CHC and its treatment in comparison with non-use of the alert system, in Valencian Community, Spain. MATERIALS AND METHODS: Decision trees and Markov model were used to evaluate the diagnosis and progression of the disease, respectively. CHC was diagnosed by serology and viral load in seropositive subjects. Epidemiological data and diagnostic costs were extracted from public sources of the Valencian Community. Probabilities, utilities and costs of model states were obtained from the literature. The impact on mortality and hepatic complications avoided by the implementation of the alert were estimated, and efficiency was measured as an incremental cost-utility ratio (ICUR) based on quality-adjusted life years (QALYs) and the costs of both alternatives. RESULTS: The EHR alert detected 269,548 patients, of whom 1,331 had CHC (vs. 23 patients with non-alert). Over the patients' lifetime, the alert would prevent 93% of decompensated cirrhosis cases, 87% of hepatocellular carcinomas, 90% of liver transplants, and 89% of liver related deaths compared to non-use of the alert system. In addition, it would obtain an additional 3.3 QALY per patient, with an incremental cost of €10,880 and an ICUR of €3,321. CONCLUSIONS: The implementation of an age-based EHR alert in primary care to detect patients with CHC reduces hepatic complications and mortality and is an efficient strategy.

Easy clinical predictor for low BCAA to tyrosine ratio in chronic liver disease patients with hepatocellular carcinoma: Usefulness of ALBI score as nutritional prognostic marker.

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

Clinical outcomes of coronavirus disease 2019 in patients with pre-existing liver diseases: A multicenter study in South Korea.

BACKGROUND/AIMS: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
. METHODS: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
. RESULTS: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20-17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04-9.30; P=0.042) in COVID-19 patients.
. CONCLUSION: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

Estimates of the global reduction in liver disease-related mortality with increased coffee consumption: an analysis of the Global Burden of Disease Dataset.

BACKGROUND: Epidemiological data suggest that coffee has a dose-dependent protective effect on liver-related mortality. AIM: To estimate the potential impact of increased per capita coffee consumption on global liver-related mortality. METHODS: Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver-related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/ day (RR 0.54, 95% CI 0.42-0.69) and ≥4 cups/ day (RR 0.29, 95% CI 0.17-0.50), adjusted for confounders and tested model assumptions using sensitivity analyses. RESULTS: Worldwide, there were an estimated 1,240,201 (95% CI 118 4300-1 354 410) adult liver-related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/ 100 000 population/ year (all ages, both genders; IQR 11-21 deaths per 100 000). If all countries with per capita coffee intake ≤2 cups/ day increased to >2 cups/ day, the predicted total number of liver-related deaths would have been 630 947 in 2016 (95% CI 629 693-631 861) with 452 861 (95% CI 451 948-454 116) deaths averted (PPR 7.8 liver-related deaths/ 100 000/ year). If per capita consumption was ≥ 4 cups/ day, the predicted number of liver-related deaths in 2016 would have been 360 523 (95% CI 359 825-361 992) with 723 287 (95% CI 721 817-723 984) deaths averted (PPR 12.1 liver-related deaths/100 000/year). CONCLUSION: Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver-related deaths annually if the impact of coffee on liver-related mortality is confirmed in clinical trials.

Prospective Investigation of Serum Metabolites, Coffee Drinking, Liver Cancer Incidence, and Liver Disease Mortality.

BACKGROUND: Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development. METHODS: We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes. RESULTS: Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection. CONCLUSIONS: A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.

Coffee consumption and liver-related hospitalizations and deaths in the ARIC study.

BACKGROUND/OBJECTIVES: Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths. SUBJECTS/METHODS: We conducted a prospective analysis on 14,208 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987-89) and visit 3 (1993-95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form. RESULTS: There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥ 3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥ 3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63-0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates. CONCLUSIONS: Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.

Comparison of Early Morbidity and Mortality Between Sleeve Gastrectomy and Gastric Bypass in High-Risk Patients for Liver Disease: Analysis of American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Chronic liver disease is prevalent in obese patients presenting for bariatric surgery and is associated with increased postoperative morbidity and mortality (M&M). There are no comparative studies on the safety of different types of bariatric operations in this subset of patients. OBJECTIVE: The aim of this study is to compare the 30-day postoperative M&M between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-Y-gastric bypass (LRYGB) in the subset of patients with a model of end-stage liver disease (MELD) score ≥ 8. METHODS: Data for LSG and LRYGB were extracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from years 2012 and 2013. MELD score was calculated using serum creatinine, bilirubin, INR, and sodium. Postoperative M&M were assessed in patients with a score ≥ 8 and compared for the type of operation. This was followed by analysis for MELD subcategories. Multiple logistic regression was performed to adjust for confounders. RESULTS: Out of 34,169, 9.8% of cases had MELD ≥ 8 and were included. Primary endpoint, 30-day M&M, was significantly lower post-LSG (9.5%) compared to LRYGB (14.7%); [AOR = 0.66(0.53, 0.83)]. Superficial wound infection, prolonged hospital stay, and unplanned readmission were more common in LRYGB. M&M post-LRYGB (30.6%) was significantly higher than LSG (15.7%) among MELD15-19 subgroup analysis. CONCLUSION: LRYGB is associated with a higher postoperative risk than LSG in patients with MELD ≥ 8. The difference in postoperative complications between procedures was magnified with higher MELD. This suggests that LSG might be a safer option in morbidly obese patients with higher MELD scores, especially above 15.

Vitamin D supplementation for chronic liver diseases in adults.

BACKGROUND: Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017. SELECTION CRITERIA: Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE. MAIN RESULTS: We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D3, one trial (18 men; mean age 61 years) with three intervention groups tested vitamin D2 and 25-dihydroxyvitamin D in separate groups, and three trials (185 participants; 55% women; mean age 55 years) tested 1,25-dihydroxyvitamin D. Seven trials used placebo, and eight trials used no intervention in the control group.The effect of vitamin D on all-cause mortality at the end of follow-up is uncertain because the results were imprecise (Peto OR 0.70, 95% CI 0.09 to 5.38; I2 = 32%; 15 trials; 1034 participants; very low quality evidence). Trial Sequential Analysis on all-cause mortality was performed based on a mortality rate in the control group of 10%, a relative risk reduction of 28% in the experimental intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z-curve did not cross the trial sequential monitoring boundary for benefit or harm after the 15th trial, and the Trial Sequential Analyses-adjusted CI was 0.00 to 2534.The effect of vitamin D on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) and on serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants), myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants), and thyroiditis (RR 0.33 95% CI 0.01 to 7.91; 1 trial; 68 participants) is uncertain because the results were imprecise. The evidence on all these outcomes is of very low quality. The effect of vitamin D3 on non-serious adverse events such as glossitis (RR 3.70, 95% CI 0.16 to 87.6; 1 trial; 65 participants; very low quality of evidence) is uncertain because the result was imprecise.Due to few data, we did not conduct Trial Sequential Analysis on liver-related mortality, and serious and non-serious adverse events.We found no data on liver-related morbidity and health-related quality of life in the randomised trials included in this review. AUTHORS' CONCLUSIONS: We are uncertain as to whether vitamin D supplements in the form of vitamin D3, vitamin D2, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D have important effect on all-cause mortality, liver-related mortality, or on serious or non-serious adverse events because the results were imprecise. There is no evidence on the effect of vitamin D supplementation on liver-related morbidity and health-related quality of life. Our conclusions are based on few trials with an insufficient number of participants and on lack of data on clinically important outcomes. In addition, the analysed trials are at high risk of bias with significant intertrial heterogeneity. The overall quality of evidence is very low.

Tumor necrosis factor-inducible gene 6 protein ameliorates chronic liver damage by promoting autophagy formation in mice.

Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0.1% ethionine (MCDE) for 2 weeks were injected with TSG-6 (the M+TSG-6 group) or saline (the M+V group) and fed with MCDE for 2 additional weeks. Histomorphological evidence of injury and increased levels of liver enzymes were evident in MCDE-treated mice, whereas these symptoms were ameliorated in the M+TSG-6 group. Livers from this group contained less active caspase-3 and more Ki67-positive hepatocytic cells than the M+V group. The autophagy markers ATG3, ATG7, LC3-II, LAMP2A and RAB7 were elevated in the M+TSG-6 group compared with those in the M+V group. Immunostaining for LC3 and RAB7 and electron microscopy analysis showed the accumulation of autophagy structures in the M+TSG-6 group. TSG-6 also blocked both tunicamycin- and palmitate-induced apoptosis of hepatocytes and increased their viability by inducing autophagy formation in these cells. An autophagy inhibitor suppressed TSG-6-mediated autophagy in the injured hepatocytes and livers of MCDE-treated mice. These results therefore demonstrate that TSG-6 protects hepatocytes from damage by enhancing autophagy influx and contributes to liver regeneration, suggesting that TSG-6 has therapeutic potential for the treatment of liver diseases.

Association of coffee intake with reduced incidence of liver cancer and death from chronic liver disease in the US multiethnic cohort.

BACKGROUND & AIMS: Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC) and chronic liver disease (CLD), but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee intake with HCC and CLD in 162,022 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the US Multiethnic Cohort (MEC). METHODS: We collected data from the MEC, a population-based prospective cohort study of >215,000 men and women from Hawaii and California, assembled in 1993-1996. Participants reported coffee consumption and other dietary and lifestyle factors when they joined the study. During an 18-year follow-up period, there were 451 incident cases of HCC and 654 deaths from CLD. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression, adjusting for known HCC risk factors. RESULTS: High levels of coffee consumption were associated with reduced risk of incident HCC and CLD mortality (Ptrend ≤ .0002). Compared with non-coffee drinkers, those who drank 2-3 cups per day had a 38% reduction in risk for HCC (RR = 0.62; 95% CI: 0.46-0.84); those who drank ≥4 cups per day had a 41% reduction in HCC risk (RR = 0.59; 95% CI: 0.35-0.99). Compared with non-coffee drinkers, participants who consumed 2-3 cups coffee per day had a 46% reduction in risk of death from CLD (RR = 0.54; 95% CI: 0.42-0.69) and those who drank ≥4 cups per day had a 71% reduction (RR = 0.29; 95% CI: 0.17-0.50). The inverse associations were similar regardless of the participants' ethnicity, sex, body mass index, smoking status, alcohol intake, or diabetes status. CONCLUSIONS: Increased coffee consumption reduces the risk of HCC and CLD in multiethnic US populations.

Association of serum α-tocopherol, ß-carotene, and retinol with liver cancer incidence and chronic liver disease mortality.

BACKGROUND: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, ß-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. METHODS: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. RESULTS: Higher ß-carotene and retinol levels were associated with less liver cancer (ß-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of ß-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. CONCLUSIONS: Our findings suggest that higher concentrations of ß-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. METHODS: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. CONCLUSION: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Morbidities and mortality in transfusion-dependent Beta-thalassemia patients (single-center experience).

BACKGROUND: The improvement of quality and duration of life of transfusion-dependent B thalassemia patients over the last years discloses several complications due to the underling disorder, iron overload and the treatment with iron chelators. Our Aim was to assess the morbidity patterns and mortality rate of transfusion-dependent thalassemia patients, and compare the outcomes in relation to age of onset, type, duration, and compliance to iron chelation therapy and frequency of blood transfusion. PROCEDURE: This retrospective study included 447 transfusion-dependent ß-thalassemia patients who attended the Thalassemia Center, Ain Shams University Children's Hospital over the last 10 years in the period between January 2000 and January 2010. Data were collected from the patients or their caregivers, as well as by reviewing follow up sheets for examinations and investigations done to detect morbidities as well as iron chelation therapies given. Determination of mortality rate and the causes of death were also done. RESULTS: Results revealed that the most common morbidities were endocrinologic (44.7%) followed by cardiovascular (41.3%) and hepatic (40.5%), then renal (4%). The different iron chelation therapy groups showed a comparable prevalence of different morbidities. The mortality rate was 1.5% and infection was the most common cause of death. The 5, 10, 20 years' survival rate among the studied patients was 80%, 50%, 20%, respectively. CONCLUSION: In the past 10 years, the survival and morbidity rates in our center have markedly improved as a result of regular blood transfusion, new iron chelators, and better compliance of the patients.

Composition of Herba Pogostemonis water extract and protection of infected mice against Salmonella Typhimurium-induced liver damage and mortality by stimulation of innate immune cells.

GC-MS analysis of a hot water extract of Herba Pogostemonis (HP) revealed the presence of 131 compounds. HP slightly inhibited Salmonella Typhimurium bacteria in culture and stimulated uptake of the bacteria into RAW 264.7 murine macrophage cells as indicated by both increased fluorescence from internalized FITC-dextran and increased colony-forming unit (CFU) counts of the lysed macrophages. Postinfection, the HP-treated cells showed lower bacterial counts than the control. HP elicited altered morphology, elevated inducible NO synthase (iNOS) mRNA, and reduced pro-inflammatory cytokine expression in macrophage cells. Salmonella induced increased expression of iNOS mRNA, cognate polypeptides, and NO. Histology of mice infected with a sublethal dose (1 × 10(4) CFU) of Salmonella showed that intraperitoneally administered HP protected against necrosis of the liver, a biomarker of in vivo salmonellosis. The lifespan of mice infected with a lethal dose (1 × 10(5) CFU) was significantly extended. These results suggest that the activity of HP against bacterial infection in mice occurs through the activation of innate immune macrophage cells. The relationship of composition of HP to bioactivity is discussed.

Antioxidant supplements for liver diseases.

BACKGROUND: Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal. OBJECTIVES: To assess the benefits and harms of antioxidant supplements for patients with liver diseases. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to January 2011. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA: We considered for inclusion randomised trials that compared antioxidant supplements (beta-carotene, vitamin A, C, E, and selenium) versus placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease, and cirrhosis (any aetiology). DATA COLLECTION AND ANALYSIS: Four authors independently selected trials for inclusion and extracted data. Outcome measures were all-cause mortality, liver-related mortality, liver-related morbidity, biochemical indices at maximum follow-up in the individual trials as well as adverse events, quality-of-life measures, and cost-effectiveness. For patients with hepatitis B or C we also considered end of treatment and sustained virological response. We conducted random-effects and fixed-effect meta-analyses. Results were presented as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI). MAIN RESULTS: Twenty randomised trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials), and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality (relative risk [RR] 0.84, 95% confidence interval [CI] 0.60 to 1.19, I(2) = 0%), or liver-related mortality (RR 0.89, 95% CI 0.39 to 2.05, I(2) = 37%). Stratification according to the type of liver disease did not affect noticeably the results. Antioxidant supplements significantly increased activity of gamma glutamyl transpeptidase (MD 24.21 IU/l, 95% CI 6.67 to 41.75, I(2) = 0%). AUTHORS' CONCLUSIONS: We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzyme activity.

Very severe psoriasis is associated with increased noncardiovascular mortality but not with increased cardiovascular risk.

It has been hypothesized that severe psoriasis is an independent risk factor for cardiovascular disease (CVD). We prospectively studied patients with severe psoriasis treated with psoralens and ultraviolet-A therapy (PUVA) who enrolled in a cohort study in 1975-1976. From 1977 to 2005, 617 of the 1,376 patients (45%) died. Compared with the general population, cohort death rates were significantly higher than expected (standard mortality ratio (SMR) = 1.1, 95% confidence interval (CI) = 1.02-1.20). The number of deaths due to CVD (SMR = 1.02, 95% CI = 0.9-1.6) was nearly identical to the expected number. Deaths due to liver disease were significantly elevated (SMR = 4.04, 95% CI = 2.76-5.70). Patients with exceptionally severe psoriasis at entry (>42% body surface area (BSA)) had a significantly increased risk of death compared with less severely affected cohort members (all-cause hazard ratio (HR) = 1.42, 95% CI = 1.18-1.69) as well as for deaths because of causes other than cancer or CVD (multivariate HR 1.56, 95% CI = 1.14-2.13). Only patients with exceptionally severe psoriasis had an increased mortality risk compared with both the general population and other cohort members with less extensive but still severe psoriasis. These increases were not significant for CVD. Our data do not support the hypothesis that severe psoriasis is an independent risk factor for CVD. However, exceptionally severe psoriasis is associated with increased all-cause mortality.

Living donor liver transplantation.

PURPOSE OF REVIEW: The widening gap between the growing number of liver transplant candidates and the supply of deceased donor organs became a strong motivation for the development of living donor liver transplantation (LDLT). LDLT has gone through its developmental phase and become an established life-saving procedure. RECENT FINDINGS: Despite the challenging nature of the technique of LDLT, there have been continuous innovations. A better understanding of complex surgical anatomy and physiologic differences of partial hepatic allografts has helped to avoid graft congestion, small-for-size syndrome, or graft hypoperfusion from portal flow steal. LDLT for patients with high Model for End-Stage Liver Disease score can achieve comparable results with deceased donor liver transplantation (DDLT). Size limitation of partial grafts can be overcome with dual grafts. The extended application of LDLT for hepatocellular carcinoma beyond Milan criteria seems feasible but at the cost of slightly compromised survival. More information has become available for prospective donors about the consequences of living liver donation in terms of psychosocial impact. SUMMARY: Although LDLT is still evolving, it has become the most effective alternative to DDLT. Proven or potential benefit of LDLT include the superior quality of the allograft despite the smaller size, selection of proper timing for transplantation and a reduced waiting time, which prevents waiting list mortality.

Protective effect of parenteral glutamine supplementation on hepatic function in very low birth weight infants.

BACKGROUND & AIMS: Hepatic dysfunction is one of the most frequent complications of parenteral nutrition. Very low birth weight (VLBW) infants are more sensitive to liver injury due to physiological immaturity. Our studies in animals showed that glutamine supplementation could attenuate TPN-associated liver injury. The aim of study was to investigate whether parenteral glutamine supplementation can improve hepatic tolerance in VLBW infants. METHODS: We performed a double-blind, randomized, and controlled clinical study to investigate whether parenteral glutamine supplementation can improve hepatic tolerance in VLBW infants. Thirty VLBW infants at two children's centers were randomly assigned to either a control group or a glutamine-supplemented group. The primary endpoints were hepatic function and mortality. The secondary endpoints were the time to achieve full enteral nutrition, episodes of gastric residuals, duration of parenteral nutrition, weight and head circumference gain, length of hospitalization, and days on ventilator. RESULTS: The serum levels of aspartate aminotransferase (AST) and total bilirubin (Tbi) were decreased after PN in the glutamine-supplemented group (P < 0.05). No deaths occurred in this study. Four infants assigned to the control group and two infants in the glutamine-supplemented group were withdrawn from the study, according to intention to treat: relative risk [RR]: 1.182; 95% confidence interval [CI]: 0.937-1.490. CONCLUSIONS: Parenteral glutamine supplementation can improve hepatic tolerance in very low birth weight infant, suggesting a hepato-protective effect.

Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

OBJECTIVES: The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated. METHODS: Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels. KEY FINDINGS: Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats. CONCLUSIONS: The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.

Nodular regenerative hyperplasia: a deleterious consequence of chemotherapy for colorectal liver metastases?

AIMS: This report describes three patients suffering from nodular regenerative hyperplasia (NRH). METHODS: These patients have received six, 16 and 20 cycles of neoadjuvant 5-fluorouracil and oxaliplatin-based chemotherapy before planned extended hepatectomy. Two patients underwent uneventful portal vein embolization to hypertrophy the future remnant liver. RESULTS: At the end of chemotherapy, liver function tests deteriorated and portal hypertension appeared in two patients, including ascites, splenomegaly and oesophageal varices. Liver biopsy was performed through a percutaneous (two patients) or a transjugular approach (one patient) and allowed the diagnosis of NRH, which was considered to be a contraindication for major liver resection in all three patients, associated with extrahepatic disease progression in one patient. All patients died from neoplastic disease progression despite further chemotherapy at 6, 17 and 31 months following the diagnosis of NRH. One patient developed liver failure and ascites at the time of death. CONCLUSIONS: Physicians should be aware of the potential occurrence and therapeutic impact of NRH in patients suffering from CRLM and treated by neoadjuvant 5FU-oxaliplatin-based chemotherapy before major liver surgery.